lec 8: steroidal anti-inflammatory agents & immunosuppresants

what are our dilation meds under 

parasympathetic cholinergics

• aka anti-cholinergic meds 

sympathetic adrenergics

what does the adrenal gland release

norepi and epi

where does dilation start

hypothalamus

senses stress, causes fear, and makes changes in our body

under times of stress what does our hypothalamus release

corticotrophin releasing factor

what stimulates the anterior pituitary gland what does the anterior pit. gland release upon being stimulated

corticotrophin releasing factor stimulates pit. gland to release corticotrophin (ACTH)

what stimulates the adrenal gland

ACTH (corticotrophin)

where does the adrenal gland sit? and what is it’s main function?

sits on top of kidneys

function: increase BP

is there a negative feedback system in the whole process from hypothalamus all the way to the adrenal gland secreting several hormones 

yes 

what are the two negative feedback loops in our sympathetic adrenergic pathway

Alpha 2 AND norepinephrine transporters

when there is too much hormones of the adrenal gland being secreted what slows it down?

the negative feedback loop

(affects how steroids are prescribed)

what does HPA stand for

hypothalamus-pituitary adrenal axis

what is the adrenal gland made up of

adrenal medulla INTERNALLY & the adrenal cortex EXTERNALLY

what does the medulla release

80% epinephrine (only when needed - during stressful conditions)

20% norepinephrine

what does the adrenal cortex release

mineralocorticoids (outer cortex)

glucocorticoids

sex hormones (right next to our medulla)

what are the basis of steroid medications & glucocorticoids

a cholesterol molecule

are steroids lipophilic

extremely which allows them to readily cross the cell membrane

what are the glucocorticoids we should be familiar with

cholesterol, progesterone, cortisol, aldosterone, testosterone, and oestradiol (estrogen) 

what are glucocorticoids responsible for

example: cortisol

homeostasis regulation

what are mineralcorticoids

example: aldosterone

fluid & electrolyte balance

what are progestins responsible for

progesterone like preggo hormones

what are androgens responsible for

growth, sexual development and behavior (male)

example: testosterone

what are estrogens responsible for

growth, sexual development and behavior (female)

example: estradiol (estrogen)

what do glucocorticoids do to our body

increase blood sugar (bc of flight or fight)

increase alertness

decrease immune response

decrease growth

what do mineralocorticoids do to our body

increase in sodium retention

decrease in potassium

increase BP

what part of the glucocorticoids outcome helps us take advantage of when we use steroid medications

the decreased immune response allows us to suppress the immune system with steroid meds when there is an unnecessary inflammatory response 

where are the nuclear receptors located

internal

why are steroid meds lipophilic

bc the nuclear receptor is inside the membrane so you need to be able to get through the phosolipid bilayer to get to the receptor and steroids are derived from cholesterol, which is also lipophilic.  

gimme the steroid mechanism of action pathway in full detail

a steroid hormone gets past the plasma membrane

binds to the steroid receptor in the plasma

gets into the nucleus and affects translation and transcription 

release a new protein called lipomodulin (aka lipocortin) 

what inhibits phospholipase A2

lipomodulin (lipocortin)

what fuels the arachidonic acid pathway

PLA2 (phospholipase A2)

what transforms the phospholipid membrane into arachidonic acid

phospholipase A2 (PLA2)

what is underneath the arachidonic acid pathway

cyclooxygenase and lipooxygenase

what does cyclooxygenase (COX1 & COX2) produce

depending on if it is COX1 or COX2, it will make either prostaglandins or thromboxane

what does lipoxygenase form

leukotrienes and HETEs

(increase mucus and airway contraction)

what is important in respiratory medicine

leuokotrienes & HETEs

causes bronchoconstriction, asthma, and ARDs (acute respiratory diseases)

what are prostaglandins responsible for

inflammation, pain, edema, decreased platelet aggregation, and vasodilation 

what are thromboxanes responsible for

they are opposite of prostaglandins

they increase platelet aggregation and cause vasoconstriction

what do corticosteroids do

when they are able to get into the nucleus and cause the production of lipomodulin and lipocortin they inhibit phosolipase A2 from converting the phospholipid membrane into arachidonic acid

can you inhibit 100% of everything

no

what do NSAIDs inhibit

COX1 or COX2 (depends on their preference)

what inhibits lipooxygenase

zileuton

primarily use in respiratory diseases

(could be potentially for food allergies but NOT YET)

what prevents leukotrienes from doing their job

montelukast

true or false: zileuton prevents the formation of leukotrienes from lipooxygenase and montelukast prevents the leukotrienes actions from happening so you dont get bronchoconstriction (airways remain open for breathing)

true

can you use zileuton and montelukast for acute asthma attacks

no

once youve already had bronchoconstriction ur done for

what can you use during an acute asthma attack

rescue inhaler like albuterol

beta2 sympathetic agonist 

what are prostaglandins a byproduct of

the arachidonic acid pathway and type 1 hypersensitivity rxns

what is released during mast cell degranulation

histamines, leuokotrines and other mediators like prostaglandins

once prostaglandins are released what happens

WBCs are normally inside our blood vessels but when they get outside that is when we experience inflammation 

under infections and inflammatory processes, what happens to our WBCs

they get outta the bloodstream and go where they needa go

this process is known as white blood cell extravasation with release of pro-inflammatory mediators like prostaglandins and interleukins

how do you get cells and flare

when WBCs are in the anterior chamber (they left the ciliary body) bc they left their blood vessel and theyre on their way to fix an issue

what is MMP-2

“constitutive; tissue remodeling”

always there

break things down when needed

supposed to be there

what is MMP-9

“inducible; pro-inflammtory”

not supposed to be there

once smth sets it off, MMP-9 is produced and theres a lot of tissue destruction

• causes more issues/destruction in order to help or fix the issue

theyre not bad (sometimes theyre needed)

what happens when you have toooo much MMP-9

inflammation

what is inflammation

calor - heat

rubor - redness

tumor - swelling

dolor - pain

functio laesa - loss of function

what is typical of an allergic response

redness, swelling, and itch

when it comes to inflammation what happens

red, itch, swell (all allergy stuff) PLUS heat and pain and eventually loss of function

how do you get inflammation

infection

mechanical trauma

pronounced or exaggerated immune response (hypersensitivity rxns)

chemical toxicity

radiation toxicity 

do steroids cure the immune response

no they just control inflammation

need to rx smth with a steroid as well in order to suppress inflammation & fix the issue